Allergenic Extract, Standardized Mites

Name: Allergenic Extract, Standardized Mites

Dosage Forms and Strengths

For immunotherapy, concentrated extracts are diluted in normal saline, buffered saline, albumin saline or 10% glycerosaline. For intradermal testing extracts may be diluted in normal saline, buffered saline, or albumin saline.

Greer Standardized Mite Extract D. farinae and Greer Standardized Mite Extract D. pteronyssinus are supplied as stock concentrates containing 10,000 Allergy Unit/mL and Greer Standardized Mite Extract mixture (D. farinae and D. pteronyssinus) is supplied as a stock mixture concentrate containing 5,000 Allergy Units/mL of each species for use in percutaneous skin testing.

Greer Standardized Mite Extract D. farinae and Greer Standardized Mite Extract D. pteronyssinus are supplied as stock concentrates containing 5,000, 10,000, or 30,000 Allergy Unit/mL. Greer Standardized Mite Extract mixture (D. farinae and D. pteronyssinus) is supplied as a stock mixture concentrate containing 5,000 and 15,000 Allergy Units/mL of each species for use in intradermal testing and immunotherapy.

Warnings and Precautions

Serious Systemic Reactions

All concentrates of Greer Standardized Mite Extracts have the ability during skin testing and immunotherapy to elicit serious systemic reactions including anaphylactic shock and death [see Adverse Reactions (6)].

A review of the literature indicates that the incidence of near-fatal reactions to immunotherapy, defined as severe respiratory compromise, hypotension, or both, and requiring emergency treatment with epinephrine, has been estimated as 5.4 events per million injections in a 10-year retrospective survey of allergists.3 Fatalities from immunotherapy injections have been estimated to occur at a rate of approximately one death per 2.0 to 2.8 million injections in 4-, 10- and 12-year retrospective surveys of allergists.4-6

Because of the danger of serious reactions, caution is required in testing and treating high risk patients and those with medical conditions that reduce their ability to survive a serious systemic adverse event.

High-risk patients are defined as those patients:

  • with labile or steroid-dependent asthma, particularly in those suffering an exacerbation of their symptoms at the time of extract administration;
  • with extreme sensitivity to a particular allergen(s);
  • who are currently using beta blockers;
  • who are receiving an accelerated immunotherapy build-up schedule (e.g., rush immunotherapy);
  • who are being changed from one allergenic extract to another;
  • who are receiving high doses of allergenic extracts.

High risk patients have had fatal reactions. In addition, patients not high-risk but on beta blockers have had fatal reactions because beta blockers interfere with beta adrenergics such as epinephrine used in treatment or anaphylaxis.

Patients should be kept under observation for a minimum of 30 minutes after receiving allergenic extracts so that any adverse reaction can be observed and properly handled.2

Medications to treat systemic reactions, as well as emergency equipment should be available for immediate use. Extracts must only be administered by persons who are aware of the risk of systemic reactions, including anaphylaxis; are capable of handling such reactions; and have the necessary drugs and equipment on hand to do so.

Patients on Beta Blockers

Patients receiving beta blockers may be unresponsive to the usual doses of epinephrine used to treat serious systemic reactions, including anaphylaxis. Inhalant allergy immunotherapy should be approached with caution in patients taking beta blockers. The risks of anaphylaxis in these patients should be carefully weighed against the benefits of immunotherapy [see Drug Interactions (7.1)].

Autoimmune Disease

Immunotherapy should be given cautiously to patients with other immunologic diseases and only if the risk from exposure to the allergen is greater than the risk of exacerbating the underlying disorder2.

Drug Interactions

Beta Adrenergic Drugs

Patients receiving beta blocker drugs may not be responsive to beta adrenergic drugs used to treat anaphylaxis10, and may wish to temporarily postpone treatment day of skin testing. All such decisions should be made in consultation with the physician. [see Warnings and Precautions (5.2)].

Antihistamines1

Skin testing with allergenic extracts should not be performed within 2-3 days of first-generation H1-histamine receptor blockers (e.g., clemastine, diphenhydramine) and within 3 to 10 days of second-generation antihistamines (e.g., loratadine, terfenadine), except for astemizole, which requires an interval of 30-60 days between allergenic extract exposure and use. These products suppress histamine skin test reactions and could mask a positive response.

Topical Corticosteroids and Topical Anesthetics1

Topical corticosteroids may suppress skin reactivity and should be discontinued at the skin test site for at least 2-3 weeks before skin testing. Topical local anesthetics may suppress flare responses and should be avoided at skin test sites.

Tricyclic Antidepressants1

Tricyclic antidepressants can have potent antihistamine effects and will affect skin testing. Since use of tricyclics may alter skin test results, dosing for both skin testing and immunotherapy should be done with caution. If tricyclic medication has been recently discontinued, allow 7-14 days prior to skin testing to obviate the antihistamine effect. The risk of anaphylaxis in these patients should be carefully weighed against the risks and benefits of stopping tricyclics.

Other Drugs

The suppressive action of other drugs should be considered and emphasizes the need for a histamine positive-control test.

Use in specific populations

Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with Greer Standardized Mite Extracts. It is also not known whether Greer Standardized Mite Extracts can cause fetal harm when administered to a pregnant woman or whether they can affect reproduction capacity. Standardized Mite Extracts should be given to a pregnant woman only if clearly needed.

Studies have not been performed in animals to determine whether extracts affect fertility in males or females, have teratogenic potential, or have other adverse affects on the fetus. Exercise caution in testing or treating pregnant females because a systemic reaction may cause maternal cardiovascular compromise leading to fetal distress with sequelae.

Nursing Mothers

It is not known whether allergenic extracts or their antigens are excreted in human milk. Because many drugs are excreted in human milk, exercise caution when extracts are administered to a nursing woman.

Pediatric Use

No studies have systematically examined differences in response to immunotherapy among child and adult patients. Children appear to tolerate injections of allergenic extracts very well.2 Very young children (under age 5) can have difficulty cooperating with an immunotherapy program and for this reason, the physician should consider the benefits and risks of immunotherapy and indiviualize treatment in patients under the age of 5 years. [See Warnings and Precautions (5) ].

Geriatric Use

Clinical studies of Greer Standardized Mite Extract did not include sufficent numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experiences has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of concomitant disease or other drug therapy including beta blockers.2

Overdosage

For all allergenic extracts the therapeutic dose varies per indiviual. If a dose exceeds the window for a particular patient this may be considered an overdose and the patient may experience anaphylaxis. Systemic reactions are uncommon after injection, but if the patient receives more extract than can be tolerated at that particular time, and begins to experience immediate hypersensitivity anaphylaxis, institute emergency treatment by trained personnel.

Overdosage may occur because of an error in the volume of extract or incorrect diluents injected. An overdose may also occur when, in addition to immunotherapy, the patient is exposed concomitantly to similar environmental allergens. In the event of a systemic reaction, the preparation of allergen and dosage schedule should be carefully reviewed.

References

  1. Bernstein IL, Li JT, Bernstein Dl, et al. Allergy dignostic testing: and updated practice parameter. Ann Allergy Asthma Immunol 2008;100:S1-148.
  2. Cox L, Li JT, Nelson H, Lockey R. Allergen immunotherapy: A practice parameter second update. J Allergy Clin Immunol 2007;120:S25-S85.
  3. Amin HS, Liss GM, Bernstein Dl. Evaluation of near-fatal reactions to allergen immunotherapy injections. J Allergy Clin Immunol 2006;117:169-75.
  4. Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol 1987;79:660-77.
  5. Reid MJ, Lockey RF, Turkeltaub PC, Platts-Mills TA. Survey of fatalities from skin testing and immunotherapy 1985-1989. J Allergy Clin Immunol 1993;92:6-15.
  6. Bernstein DI, Wanner M, Borish L, Liss GM. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol 2004;113:1129-36.
  7. Lockey RF, Nicoara-Kasti GL, Theodoropoulos DS, Bukantz SC. Systemic reactions and fatalities associated with allergen immunotherapy. Ann Allergy Asthma Immunol 2001;87(suppl 1):47-55.
  8. Malling HJ. Minimising the risks of allergen-specific injection immunothreapy. Drug Saf 2000;23:323-332.
  9. Greenberg MA, Kaufman CR, Gonzalez GE, et. al. Late and immediate systemic-allergic reactions to inhalant allergen immunotherapy. J Allergy Clin Immunol 1986;77:865-870.
  10. Jacobs RL, Rake GW, Jr., Fournier DC, Chilton RJ, Culver WG, Beckmann CH. Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade. J Allergy Clin Immunol 1981;68:125-7.
  11. Arlian L, Bernstein D, Bermstein L, et al. Prevalence of dust mites in the homes of people with asthma living in eight different geopgraphic areas of the United States. J Allergy Clin Immunol 1992;90:292-300.
  12. Chapman MD, Platts-Mills TA, Gabriel M, et al. Antibody response following prolonged hyposensitization with Dermatophagoides pteronyssinus extract. In Arch Allergy Appl Immunol 1980;61:431-40.
  13. Gurka G, Rocklin R. Immunologic responses during allergen-specific immunotherapy for respiratory allergy. Ann Allergy 1988;61:239-45.
  14. Voorhorst R, Spieksma FTM, Varekamp H. House Dust Atopy and the House Dust Mite. Leiden: Stafleu's Scientific Publishing Co; 1969.
  15. Maunsell K, Wraith DG, Hughes AM. Hyposensitisation in mite asthma. Lancet 1971;1:967-8.
  16. Mite Allergy Subcommittee of the Research Committee of the British Thoracic Association. A trial of house dust mite extract in bronchial asthma. Br J Dis Chest 1979;73:260-70.
  17. Abramson MJ, Puy RM, Weiner JM. Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials. Am J Respir Crit Care Med 1995; 151:969-74.
  18. Abramson M, Puy R, Weiner J. Immunotherapy in asthma: an updated systematic review. Allergy 1999;54:1022-41.
  19. Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. The Cochrane Database of Systematic Reviews 2003;CD001186.
  20. Bousquet J, Calvayrac P, Guerin B, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. I. In vivo and in vitro parameters after a short course of treatment. J Allergy Clin Immunol 1985;76:734-44.
  21. Garcia-Ortega P, Merelo A, Marrugat J, Richart C. Decrease of skin and bronchial sensitization following short-intensive scheduled immunotherapy in mite-allergic asthma. Chest 1993;103:183-7.
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